Lecture 6 - B cell Activation

Question 1

Changes in B cells after activation by antigen

Answer 1

1. Antibody secretion
2. Somatic mutation - additional diversity
3. Isotype switching

Question 2

_________ is the process responsible for changing membrane IgM to secreted IgM

Answer 2

Alternative RNA processing

Question 3

Transmembrane IgM is expressed by ________, while secreted IgM is expresed by ___________

Answer 3

Transmembrane = Unactivated B cell

Secreted = Activated B cell (differentiated into a plasma cell)

Question 4

In somatic hypermutation what do the red bars indicate? Where are they most common?

Answer 4

Nucleotide substitutions

Typically occur in the hypervariable regions (CDR) of the V domain

Question 5

The CDR regions of the heavy and light chains make up the…

Answer 5

antigen binding site

Question 6

Somatic hypermutation is mediated by…

Answer 6

activation-induced cytidine deaminase

(C–>U)

Question 7

The light chain V region is made of _____ DNA segments and ______ DNA segments

Answer 7

Framework (FR)

Hypervariable (HV)

Question 8

Isotype switching results in

Answer 8

Ig molecules with different C regions but identical antigen specificity

Question 9

Isotype switching is mediated by

Answer 9

AID

activation induced cytosine deaminase

Question 10

AID selectively targets the ______ regions during isotype switching

Answer 10

S_µ and S _γ1 switch regions

Question 11

There is no switch region between…

Why?

Answer 11

Cµ + Cδ

Because the B cell can express both via alternative splicing

Question 12

What happens after AID nicks the DNA in the switch regions during isotype switching?

Answer 12

The DNA inbetween the switch regions is looped out, and the immunoglobulin gene is made into a functional molecule (IgG1, in the figure given)

Question 13

This molecule is turned on upon B cell activation

Answer 13

Activation-induced cytosine deaminase

AID

Question 14

A particular isotype switching is determined by…

Answer 14

T_H cell cytokines

Question 15

Effector functions of antibodies

Answer 15

Neutralization

Opsonization

Complement activation

Question 16

Antibody mediated opsonization involves…

Answer 16

IG binds to bacteria, and the Fc region binds to the FcR on Macrophage to facilitate phagocytosis

Question 17

Complement activation by antibodies leads to…

Answer 17

• opsonization
• Cell death via proteolytic enzymes
• Inflammation

Question 18

IgM conformational structure

What different thing does it contain?

Answer 18

Monomer = membrane, Pentamer = secretion

Contains a stabilizer protein /J-chain in the middle of its pentamer (NOT the J chain from VDJ recombination)

Question 19

IgM binding properties

Answer 19

Low affinity

but high avidity due to its 10 binding sites

Question 20

Functions of IgM (3)

Answer 20

1. 1^st secreted during immune response
2. Activates complement (& agglutination)
3. Transported into mucosal secretions

Question 21

IgM doesn’t need….

Answer 21

Coomb’s reagent to crosslink

Question 22

IgM is present on the membrane of…

Answer 22

naive B cells

Question 23

Highest Ig (concentration) in serum is ____

Answer 23

IgG

Question 24

what are the subclasses of IgG, and what function do they differ in?

Answer 24

IgG1-4

they activate complement at different rates (3>1>2)

*IgG4 does not activate complement

Question 25

IgG molecules bind to __ receptors…on which cells?

Answer 25

Fc-gamma receptors

on neutrophils, MQ, and NK cells

Question 26

IgG differ in the structure of…

Answer 26

the hinge region

IgG3 has the most flexibility but is most susceptible to proteolytic cleavage (effectively lowering its half-life)

Question 27

IgG4 is functionally…

Answer 27

monovalent

can dissociate and recombine to a bivalent molecule (binds two epitopes)

Question 28

Bivalent IgG4 has a ___ avidity than monovalent.

Why?

Answer 28

Lower avidity

because it can only bind one of each type of antigen instead of two (monovalent has two CDR regions that have the same specificity)

Question 29

IgA subclasses and structures

Answer 29

IgA1 = Monomer (mostly)

IgA2 = Dimer

Secretory IgA is usually a dimer

Question 30

IgA dimer is connected via

Answer 30

a J chain (different from VDJ)

Question 31

IgA function

Answer 31

Neurtralization of microorganisms

NOT an effected complement inducer

Question 32

Strep pneumo, H. influenzae, and Mengingococcus all produce ____ that gives them tissue access

Answer 32

IgA proteases

Question 33

IgE structurally contains…

Answer 33

an extra C_H domain

NO hinge region

Question 34

IgE is usually in LOW concentrations, but is present in higher amounts in people with…

Answer 34

allergies and helminth infections

Question 35

IgE binds to ___ on what cells?

Answer 35

FcE receptors

on mast cells and basophils

induces degranulation

Question 36

IgD is present with _____ on what cells?

Answer 36

with IgM

on naive mature B cells

Question 37

Highest serum immunoglobulin

Answer 37

IgG1

Question 38

Lowest serum Ig isotype

Answer 38

IgD

Question 39

IgD secreting plasma cells are located where?

Answer 39

URT

Question 40

___ is pretty much the only isotype to be transported across epithelium

Answer 40

IgA

Question 41

Isotypes:

M, G1, G3 are more for…

G1,2,3,4 + A are more for

Answer 41

M, G1, G3 = Complement

G1,2,3,4 + A = Neutralization

Question 42

What are the two reversible and regulated steps in B cell life cycle

Answer 42

• Activation of coexpression of IgM and IgD on surface
• Antibody synthesis changes from membrane Ig to secreted

Question 43

The five irreversible steps in B cell life cycle

Answer 43

1. V region assembly
2. Junctional diversity (imprecise joining & P/N NT insertion)
3. Assembly of transcriptional machinery (promoter and enhancer brought together)
4. Somatic hypermutation
5. Isotype switching